Table 18 Condensed information of various heterocyclic analogues as estrogen alpha receptor antagonists
From: Estrogen alpha receptor antagonists for the treatment of breast cancer: a review
Sr. No. | Comp. | Breast cancer cell lines/structural similarity IC50 values | Reference drugs with IC50 value | Molecular docking | In vitro/vivo study | Mechanism | References | ||
|---|---|---|---|---|---|---|---|---|---|
Diphenylmethane, Diphenylmethyelene, Diphenylheptane, Diphenyl amine analogs and triarylethylene analogs | |||||||||
1. | 1 | On ER-α 4.9 nM | In presence of 0.5 nM 17β-estradiol | Autodock program 4.2 | In silico |  | Mauryama et al. [14] | ||
2. | 8 | MCF-7 (62.2 nM) | (E,Z) nor endofexin (10.22 ± 32.7) | GOLD 3.0 | In vitro | Antagonize the PGR mRNA expression level | Zhao et al. [16] | ||
3. | 20–22 |  | MCF-7 | Tamoxifen, (> 50) | CDOCKER docking algorithm | In vitro | Suppressed the expression of c-myc, MMP-9 and caveolin | Kaur et al. [26] | |
20 | 11.4 ± 4.2 µM | ||||||||
21 | 16.9 ± 7.7 µM | ||||||||
22 | 12.2 ± 5.3 µM | ||||||||
4. | 46 | MCF-7 (450 nM) | 17 β estradiol | Molecular operating environment | In vitro | Suppression of ER alpha transcriptional activity | Eto et al. [42] | ||
5. | 55 | MCF-7 (1.3 ×10−7 M) | Tamoxifen (2.1 × 10−6 M) | – | In vitro | – | Ohta et al. [46] | ||
Coumarin analogs | |||||||||
6. | 12 | MCF-7, GI50 < 10 | Tamoxifen (29.4 µg/ml) | Glide v 5.8 | In vitro | Inhibit ER functional activity | Mokale et al. [20] | ||
7. | 13–14 | MCF-7 | Tamoxifen (11.35 ± 3.13 µM) | Discover studies3.0/CDOCKER protocol | In vitro | Antagonistic confirmation as that of OHT | Luo et al. [21] | ||
13 | 4.52 ± 2.47 | ||||||||
14 | 7.31 ± 2.12 | ||||||||
Steriodal analogs | |||||||||
8. | 16 | MCF-7, 5.49 µM | Tamoxifen (0.0075 µM) | – | In vitro | – | Alsayari et al. [23] | ||
9. | 51–54 | MCF-7 (nm) | Tamoxifen (200 nm) Fulvestrant (2 nm) | Insight II modeling software | In silico | Inhibitory activity for ER α transactivation | Jiang et al. [45] | ||
51 | 50 | ||||||||
52 | 50 | ||||||||
53 | 100 | ||||||||
54 | 50 | ||||||||
10. | 18 | 18 | MDA-MB-239) | T47D | Reservatol | Computational docking modeling | In vitro | H–bonding interactions and tight binding with active sites of ER alpha | Siddqui et al. [24] |
a | 21 µM | 32 µM | 66 µM | ||||||
b | 29 µM | 44 µM | 76 µM | ||||||
11. | 47 | MCF-7 (6.8 ± 0.7 µM) | Tamoxifen, 5.3 ± 0.6 µM | DOCK 6.5 | In vitro | Inhibit ER transcriptional activity | Kuzestnov et al. [43] | ||
12. | 56–57 | MCF-7 | 2-methoxy estradiol (6.01 µM) | – | In vitro | G2/M cell cycle arrest by disrupting normal microtubule functions | Lao et al. [47] | ||
56 | 2.73 µM | ||||||||
57 | 7.75 µM | ||||||||
Quinoline, Isoquinolne and Isoflavone analogs | |||||||||
13. | 32 | MCF-7, (11 µM) | – | – | In vitro | – | Bharatkumar et al. [34] | ||
14. | 28 | MCF-7, (0.5 µM) | Tamoxifen (13.9 µM) | Discovery Studio2.5/CDOCK protocol | In vitro | ER-α and VGFR-α inhibitory activity | Tang et al. [31] | ||
15. | 33–35 | Aromatase inhibitory activity | Ketoconazole | GOLD 5.0. | In vitro | Inhibitory activity against aromatase | Bonfield et al. [35] | ||
33 | 2.4 µM | ||||||||
34 | 0.26 µM | ||||||||
35 | 5.8 µM | ||||||||
16. | 43–45 | MCF-7 | Genistein (14 µM) | eHiTS docking prgram | In vitro | Inhibiting ER α messenger RNA expression | Marik et al. [41] | ||
43 | 1.0 µM | ||||||||
44 | 0.8 µM | ||||||||
45 | 1.2 µM | ||||||||
17. | 48–50 | MCF-7 (µg/ml) | Tamoxifen (3.99 µg/ml) | HYBRID V 3.01 | In vitro | Microtubule destabilizing agreement | Suresh et al. [44] | ||
48 | 0.2 | ||||||||
49 | 0.61 | ||||||||
50 | 0.2 | ||||||||
Indole analogs | |||||||||
18. | 36–37 | T47D | Bazedoxifene (16.43 ± 0.94 µM) | Glide XP with vdW 0.8 | In vitro | Altering the m-RNA and ER-α receptor expression,thus inhibiting further transactivation and signaling | Singla et al. [36] | ||
36 | 16.51 ± 0.75 µM | ||||||||
37 | 17.94 ± 1.0 µM | ||||||||
19. | 38–39 | T47D | Bazedoxifene (16.43 ± 0.94 µM) | Glide XP with vdW 0.8 | In vitro | Altered the mRNA and ER-α receptor protein expression, thus preventing the further transcriptional activation and signaling pathway | Singla et al. [37] | ||
38 | 4.99 ± 0.60 µM | ||||||||
39 | 15.48 ± 0.10 µM | ||||||||
20. | 23–24 | MCF-7 |  | Fred 3.0.1 | In vitro | Inducing apoptosis | Kelley et al. [27] | ||
23 | 2.7 µM | Tamoxifen | |||||||
24 | 1.8 µM | Comberstatin | |||||||
21. | 41 | MCF-7 | Tamoxifen (OHT) | GOLD 5.0.1 | In vitro | Inhibit ER transcription activity and gene expression | Lappano et al. [39] | ||
Furan derivatives and Bis(hydroxyphenyl) azoles | |||||||||
22. | 9 | MCF-7, (0.022 µM) | Fulvestrant, (0.004 µM) | – | In vitro | – | Zimmermann et al. [17] | ||
23. | 10 | MCF-7, (43.08 µM) | Tamoxifen (12.35 µM) | Schrodinger suite 2010 | In vitro | pi–pi conjugate interactins | Li et al. [18] | ||
24. | 31 | T47D, (0.31 µM) | – | GOLD 3.0 | In vitro | Non steroidal inhibitors of 17β-HSD1 | Bey et al. [33] | ||
25. | 42 | ER alpha, (6.5 × 10−8 M) | Tamoxifen | – | In vitro | Inhibit the trans criptonal activity of estradiol | Mortensen et al [40] | ||
26. | 25 | 25 | MCF-7 | Tamoxifen (55.89 µM) | – | In vitro | – | Sun et al. [28] | |
a | 90.63 µM | ||||||||
b | 72.55 µM | ||||||||
27. | 26 | hER alpha | Â | SYBYL 65.2 | Â | Â | Stauffer et al. [29] | ||
28. | 29–30 | MCF-7 | Doxorubicin (0.473 µM) | – | In vitro | By affecting interaction between ERE-ER alpha | Kamal et al. [32] | ||
29 | 1.76 µM | ||||||||
30 | 2.16 µM | ||||||||
Metal based analogs | |||||||||
29. | 40 | MCF-7, (0.50 µM) | Cisplatin (16.1 µM) | – | In vitro | – | Perron et al. [38] | ||
30. | 58 | MCF-7, (1.06 µM) | – |  | In vitro | Inhibit histone deacetylase | Marinero et al. [48] | ||
Inverse agonist | |||||||||
31. | 15 | ERR alpha protein in MDA-MB-231breast Cancer cell line 0.64 ± 0.12 µM | – | Sybyl x2.0 | In vitro | Inhibit ERR alpha transcriptional activity through PDK4, Osteopontin and pS2 | Ning et al. [22] | ||
Mice (MDA-MB-231,breast tumor xenografts) 42.02% inhibition | Untreated growth tumor cell | Â | In vivo | Â | Â | ||||